Phytochemical Screening and Hepatoprotective Effect of Alhagi maurorum Boiss (Leguminosae) Against Paracetamol-Induced Hepatotoxicity in Rabbits

Purpose: To evaluate the hepatoprotective activity of aqueous-ethanol (30:70 %) extract of Alhagi maurorum Boiss. (Leguminosae) whole plant against paracetamol-induced liver injury in experimental rabbits.Methods: Aqueous-ethanol extract of Alhagi maurorum at doses of 250 mg/kg and 500 mg/kg body weight, p.o., was administered for 7 days in paracetamol (2 gm/kg, s.c.) intoxicated rabbits and compared with silymarine (50 mg/kg, p.o.)-treated rabbits. Biochemical parameters, alkaline phosphatase (ALP), serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and total bilirubin (TB) levels were recorded to investigate the degree of improvement in the conditions of the rabbits. The liver was removed, washed with normal saline and preserved in 10 % formalin and used in histopathological studies of hepatic architecture by microscopy. Phytochemical screening of the extract was also carried out.Results: The levels of biochemical parameters were increased in paracetamol intoxicated rabbits when compared with the normal group. The extract, at doses of 250 and 500 mg/kg, exhibited significant (p < 0.001) reduction in biochemical parameters (ALP, SGOT, SGPT and TB). Hepatoprotective activity was also confirmed by histopathological findings. Furthermore, the phytochemical profile of the extract revealed the presence of tannins, alkaloids, saponins and flavonoids.Conclusion: These results suggest that Alhagi maurorum extract possesses significant hepatoprotective effect against paracetamol-induced hepatotoxicity and this may be due to the presence of flavonoids and tannins.Keywords: Alhagi maurorum, Hepatoprotective, Paracetamol, Silymarin, Histopatholog

Proceedings of the Salford Postgraduate Annual Research Conference (SPARC) 2011

These proceedings bring together a selection of papers from the 2011 Salford Postgraduate Annual Research Conference(SPARC). It includes papers from PhD students in the arts and social sciences, business, computing, science and engineering, education, environment, built environment and health sciences. Contributions from Salford researchers are published here alongside papers from students at the Universities of Anglia Ruskin, Birmingham City, Chester,De Montfort, Exeter, Leeds, Liverpool, Liverpool John Moores and Manchester

Quinpirole-mediated regulation of dopamine D2 receptors inhibits glial cell-induced neuroinflammation in cortex and striatum after brain injury

Brain injury is a significant risk factor for chronic gliosis and neurodegenerative diseases. Currently, no treatment is available for neuroinflammation caused by the action of glial cells following brain injury. In this study, we investigated the quinpirole-mediated activation of dopamine D2 receptors (D2R) in a mouse model of traumatic brain injury (TBI). We also investigated the neuroprotective effects of quinpirole (a D2R agonist) against glial cell-induced neuroinflammation secondary to TBI in adult mice. After the brain injury, we injected quinpirole into the TBI mice at a dose of 1 mg/kg daily intraperitoneally for 7 days. Our results showed suppression of D2R expression and deregulation of downstream signaling molecules in ipsilateral cortex and striatum after TBI on day 7. Quinpirole administration regulated D2R expression and significantly reduced glial cell-induced neuroinflammation via the D2R/Akt/glycogen synthase kinase 3 beta (GSK3-β) signaling pathway after TBI. Quinpirole treatment concomitantly attenuated increase in glial cells, neuronal apoptosis, synaptic dysfunction, and regulated proteins associated with the blood−brain barrier, together with the recovery of lesion volume in the TBI mouse model. Additionally, our in vitro results confirmed that quinpirole reversed the microglial condition media complex-mediated deleterious effects and regulated D2R levels in HT22 cells. This study showed that quinpirole administration after TBI reduced secondary brain injury-induced glial cell activation and neuroinflammation via regulation of the D2R/Akt/GSK3-β signaling pathways. Our study suggests that quinpirole may be a safe therapeutic agent against TBI-induced neurodegeneration

Vanillic acid, a bioactive phenolic compound, counteracts LPS-induced neurotoxicity by regulating c-Jun N-terminal kinase in mouse brain

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor signaling event, has been associated with several human illnesses, including neurodegenerative diseases, particularly in Alzheimer’s disease (AD). Vanillic acid (V.A), a flavoring agent, is a benzoic acid derivative having a broad range of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the underlying molecular mechanisms of V.A in exerting neuroprotection are not well investigated. The present study aims to explore the neuroprotective effects of V.A against lipopolysaccharides (LPS)-induced neuroinflammation, amyloidogenesis, synaptic/memory dysfunction, and neurodegeneration in mice brain. Behavioral tests and biochemical and immunofluorescence assays were applied. Our results indicated increased expression of RAGE and its downstream phospho-c-Jun n-terminal kinase (p-JNK) in the LPS-alone treated group, which was significantly reduced in the V.A + LPS co-treated group. We also found that systemic administration of LPS-injection induced glial cells (microglia and astrocytes) activation and significantly increased expression level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) and secretion of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL1-β), and cyclooxygenase (COX-2). However, V.A + LPS co-treatment significantly inhibited the LPS-induced activation of glial cells and neuroinflammatory mediators. Moreover, we also noted that V.A treatment significantly attenuated LPS-induced increases in the expression of AD markers, such as β-site amyloid precursor protein (APP)−cleaving enzyme 1 (BACE1) and amyloid-β (Aβ). Furthermore, V.A treatment significantly reversed LPS-induced synaptic loss via enhancing the expression level of pre- and post-synaptic markers (PSD-95 and SYP), and improved memory performance in LPS-alone treated group. Taken together; we suggest that neuroprotective effects of V.A against LPS-induced neurotoxicity might be via inhibition of LPS/RAGE mediated JNK signaling pathway; and encourage future studies that V.A would be a potential neuroprotective and neurotherapeutic candidate in various neurological disorders

AAV2-Mediated Combined Subretinal Delivery of IFN-α and IL-4 Reduces the Severity of Experimental Autoimmune Uveoretinitis

We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×107 vg), AAV2.IL-4 alone (3.55×107 vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×107 vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response

A Friendly Relationship between Endophytic Fungi and Medicinal Plants: A Systematic Review

Endophytic fungi or endophytes exist widely inside the healthy tissues of living plants, and are important components of plant micro-ecosystems. Over the long period of evolution, some co-existing endophytes and their host plants have established a special relationship with one and another, which can significantly influence the formation of metabolic products in plants, then affect quality and quantity of crude drugs derived from medicinal plants. This paper will focus on the increasing knowledge of relationships between endophytic fungi and medicinal plants through reviewing of published research data obtained from the last 30 years. The analytical results indicate that the distribution and population structure of endophytes can be considerably affected by factors, such as the genetic background, age, and environmental conditions of their hosts. On the other hand, the endophytic fungi can also confer profound impacts on their host plants by enhancing their growth, increasing their fitness, strengthening their tolerances to abiotic and biotic stresses, and promoting their accumulation of secondary metabolites. All the changes are very important for the production of bioactive components in their hosts. Hence, it is essential to understand such relationships between endophytic fungi and their host medicinal plants. Such knowledge can be well exploited and applied for the production of better and more drugs from medicinal plants

Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice

Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment